Acute poisoning with sarin causes alteration in oxidative homeostasis and biochemical markers in Wistar rats

Abstract

Sarin is a potent inhibitor of acetylcholinesterase (AChE). It is known as an agent of chemical warfare and is one of a number of nerve agents misused for chemical terrorism, e.g. on the Tokyo subway attacks. Though effect of sarin on the cholinergic system is well-known, long-term adverse effects and the role of oxidative stress in sarin toxicity remain unknown. The experiment reported here was carried out on laboratory Wistar rats intramuscularly exposed to 0.5-50% of sarin LD 50 for one hour. A complex biochemical examination of plasma samples and an assessment of oxidative stress in the liver, kidney, spleen, cerebellum and frontal lobe were performed after euthanasia of the animals. By means of these biochemical markers, we were able to observe the induction of hyperglycaemia in a dose-dependent manner. Other biochemical markers such as transaminases were influenced in a non-standard manner as sarin probably acted as an inhibitor of these markers. Oxidative stress markers and an assessment of AChE activity showed an unequal impact of sarin on different tissues. Significant inhibition of AChE was found in the cerebellum and frontal lobe. Besides this, alterations in reduced glutathione, ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) were proven. In particular, an accumulation occurred of reduced glutathione in the frontal lobe, whereas depletion of FRAP was found in the kidney and spleen, and a strong increase in TBARS occurred in the spleen in a dose-dependent manner. We infer that sarin extensively influences oxidative homeostasis. Surprisingly, the central nervous system seems to be more resistant than the other organs.

Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review

“…The inhalation of sarin at levels close to LC 50 can cause increased levels of hypoxia-induced factor-1α, bronchoconstriction, and pro-inflammatory cytokine surges, which alter the lung epithelium, increase bronchosecretions, and can lead to death (Carey et al 2013; Gundavarapu et al 2014). Studies showed that acute sarin poisoning causes changes to the oxidative homeostasis and biochemical markers in rats intramuscularly injected with 50% of sarin LD 50 (Pohanka et al 2012; Abou-Qare and Abou-Donia 2001b). …”

The possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoning

“…Another group also looked at the effect of oral lipid emulsion in rats following oral exposure to malathion or chlorpyriphos, both lipophilic compounds, in different time points [12] , [101] . Since it was shown in the past that OP exposure leads to oxidative stress [1] , [71] , [92] , [106] , [111] , [140] , this group decided to focus on total antioxidant capacity (TAC) and total oxidant status (TOS) of the rat brain, as well as on immunohistochemical staining of caspase-3 as a marker for apoptosis. In the malathion study, lipid emulsion was given either immediately or with a delay of six and 12 h post-exposure [12] .…”

“…This was suggested by recently-reported reversal of severe OP-induced cardiotoxicity in a human patient by ILE [90] . Mitochondrial protection, antiapoptotic and antioxidant properties: poisoning with OP pesticides in humans and with CWAs in animals are associated with increased oxidative stress [1] , [71] , [92] , [106] , [111] , [140] and with tissue damage, apoptosis and necrosis of cells in the CNS and in other organs [29] , [74] , [87] . Mitochondrial dysfunction in the CNS and other tissues, which was found to occur in OP pesticide poisoning [74] and in nerve-agent exposure [28] , has a causal role in the elicitation of oxidative imbalance and apoptosis.…”

Biosensors for Blood Glucose and Diabetes Diagnosis: Evolution, Construction, and Current Status

“…The type of drug determines whether hyper-or hypo-glycemia occurs (Sabzghabaee et al 2011;Pohanka, Románek, and Pikula 2012). Long-term hyperglycemia may be involved in many life-threatening complications such as cardiovascular diseases, diabetic nephropathy, neuropathy, and rethinopathy.…”